Pregnancy outcome in women with transfused beta-thalassemia in France.

Because of chronic anemia, hypogonadotropic hypogonadism, and iron chelation, pregnancy in homozygous and heterozygous compound beta-thalassemia patients stays a challenge. Pregnancies of transfused beta-thalassemia women registered in the French National Registry, conducted between 1995 and 2015, are described. These pregnancies were compared with pregnancies in healthy women and to data previously published in the literature. Fifty-six pregnancies of 37 women were studied. There were 5 twin pregnancies. Assisted reproductive technologies (ART) were used in 9 pregnancies. Median term at delivery was 39 amenorrhea weeks, and median weight at birth was 2780 g. Cesarean section was performed in 53.6% of the pregnancies. There were 6 thromboembolic events, 6 serious infections, 6 pregnancy-induced hypertensions (PIH), 6 intrauterine growth retardations (IUGR), 5 severe hemorrhages, 4 gestational diabetes, 3 alloimmunizations, 2 heart diseases, and 1 pre-eclampsia. There were 5 infections and 4 osteoporosis in the first year of post-partum. ART and cesarean sections were more often used in the beta-thalassemia group, compared to control subjects. Thromboembolic events, PIH, hemorrhage at delivery, and IUGR were more frequent in the beta-thalassemia group. Time to delivery was not different, but infant weight at birth was significantly smaller in the beta-thalassemia group. In the post-partum period, global maternal complications were more frequent in the beta-thalassemia group. Pregnancy in transfused beta-thalassemia women is safe with rare obstetrical and fetal complications. Cesarean section remains often chosen, and infant weight at birth remains smaller than that in the general population, despite delivery at full term.

Ethnicity and association with ocular, systemic manifestations and prognosis in 194 patients with sarcoid uveitis.

OBJECTIVE: To determine the ophthalmological and extra-ophthalmological clinical characteristics and visual prognosis of patients with sarcoid uveitis in different ethnic groups. METHODS: We retrospectively analysed the data from patients with sarcoid uveitis seen at two departments of Ophthalmology between December 2003 and December 2017. Patients presented biopsy-proven sarcoidosis and/or presumed sarcoid uveitis based on the following criteria: compatible thoracic imaging, associated with elevated angiotensin-conversion enzyme (ACE) and/or lymphocytic alveolitis on bronchoalveolar lavage fluid analysis (> 15% lymphocytes and CD4/CD8 > 3.5). Ophthalmological and general characteristics, as well as visual and global prognoses, were compared in three pre-defined ethnic groups: White Europeans, North Africans and Afro-Caribbeans. RESULTS: A total of 194 patients were included: 145 with biopsy-proven and 49 with presumed sarcoid uveitis. Overall, 68% were White Europeans while 20.6% were North Africans and 11.3% were Afro-Caribbeans. Sixty-nine per cent were women and the median age at presentation was 52.1 years. Median ages at first ocular manifestation of the disease in Afro-Caribbeans and North Africans were respectively 34.3 and 43.1 years, while it was 57.8 years in White Europeans (p < 0.001). Ocular involvement was bilateral in 77.8% (n = 151) of the cases and nearly half of the patients had panuveitis (48.5%). Anterior uveitis was more frequent in Afro-Caribbeans (59.1%; p < 0.0001), while White Europeans presented more frequently with intermediate uveitis. There was a significantly higher frequency of systemic involvement of sarcoidosis in North Africans while White Europeans showed a higher frequency of isolated ocular involvement at onset and during follow-up. Afro-Caribbeans, who had a complete visual recovery in 72.7% of the cases, had a better visual prognosis than other ethnic groups (p = 0.025). CONCLUSION: In this large European series of sarcoid uveitis, we observed ethnicity-related differences regarding uveitis clinical presentation and visual outcome. Although good overall, the visual prognosis seems to be better in Afro-Caribbeans than in other ethnic groups.

Long-term extrapulmonary comorbidities after lung transplantation in cystic fibrosis: Update of specificities.

Lung transplantation (LT) is the standard therapeutic option for cystic fibrosis (CF) patients with end-stage lung disease. Both conditions lead to extrarespiratory complications, such as diabetes, renal insufficiency, bone disease, and cancer. The purpose of this study was to provide an update of the nonrespiratory comorbidities following LT in adult patients with CF and their specificities regarding their multisystemic underlying condition despite their younger age compared to other patients undergoing LT. Diabetes, renal insufficiency, metabolic bone disease, hypertension, liver disease, and cancer are the comorbidities considered in this review. The increase in CF adults living with a lung transplant justifies an update of knowledge for this specific situation (the prevalence of these complications, underlying risk factors), to provide better medical care and establish early diagnosis strategies.

Arthroscopic isolated capsular release for shoulder contracture after brachial plexus birth palsy: clinical outcomes in a prospective cohort of 28 children with 2 years' follow-up.

BACKGROUND: The primary objective of this study was to evaluate improvements in external rotation after isolated arthroscopic capsular release in children with shoulder contracture due to brachial plexus birth palsy. MATERIALS AND METHODS: This study included all children older than 2 years with a range of active external rotation limited to 30° or less and/or active anterior elevation (AE) limited to 90° or less secondary to brachial plexus palsy treated between 2011 and 2015. Passive glenohumeral motion, passive global (glenohumeral plus scapulothoracic) motion, active global motion for external rotation with the elbow at the side (ER1), AE, and internal rotation with the elbow at the side were recorded before and 2 years after surgery. Improvement was evaluated by comparing the preoperative and follow-up values. The operation performed was subscapularis-sparing arthroscopic capsular release. RESULTS: Thirty-five patients were included, and 28 completed 2 years of follow-up. The average changes in active global ER1, passive glenohumeral ER1, and passive global ER1 were +35° (range, -20° to +100°; P <.0001), +35° (range, +0° to +75°; P <.0001), and +26° (range, -15° to +60°; P <.0001), respectively. There were no significant changes in internal rotation with the elbow at the side or AE. The mean improvement in the aggregate Mallet score was 3.9 points (range, -3 to +9 points; P <.0001). CONCLUSIONS: For children with shoulder contracture secondary to brachial plexus palsy, subscapularis-sparing isolated capsular release improves external rotation and functional scores and avoids any loss of active internal rotation but does not improve AE.

Extended Anticoagulation for VTE: A Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) during extended anticoagulation for a VTE remains largely unknown, especially in terms of potential survival benefit. The goal of this study was to assess the effects of VKAs and DOACs on overall mortality and VTE-related mortality, as well as VTE recurrence and safety. METHODS: PubMed, EMBASE, and the Cochrane Library were searched from January 1990 through September 2018 for randomized controlled trials evaluating the effect of extended anticoagulants as secondary prevention for VTE compared with placebo. The primary outcome was the specific effects of standard-intensity VKAs and DOACs on overall mortality. RESULTS: Sixteen studies (12,458 patients) were included. DOACs were associated with a reduction in overall (risk ratio [RR], 0.48; 95% CI, 0.27-0.86; P = .01) and VTE-related (RR, 0.36; 95% CI, 0.15-0.89; P = .03) mortality, whereas VKAs were not (P > .50). Although VKAs and DOACs similarly prevented recurrent VTE, only VKAs were associated with an increased risk of major bleeding (RR, 2.67; 95% CI, 1.28-5.60; P < .01), resulting in an improved net clinical benefit for DOACs (RR, 0.25 [95% CI, 0.16-0.39; P < .01] vs 0.46 [95% CI, 0.30-0.72; P < .01]; Pinteraction = .05). CONCLUSIONS: DOACs for extended anticoagulation were associated with a significant reduction in overall mortality compared with observation alone. TRIAL REGISTRY: PROSPERO; No.: CRD42018088739; URL: https://www.crd.york.ac.uk/prospero/.

Extended anticoagulation for the secondary prevention of venous thromboembolic events: An updated network meta-analysis.

BACKGROUND: Extended treatment is preconized in a significant proportion of patients with unprovoked venous thromboembolism (VTE). However, limited direct/indirect comparisons are available to appropriately weight the benefit/risk ratio of the diverse treatments available. We aimed to compare the rate of symptomatic recurrent VTE and major bleeding (MB), the net clinical benefit (VTE+MB) and death on vitamin-K antagonist (VKA), direct oral anticoagulants (DOAC) and antiplatelet drugs for extended anticoagulation. METHODS: A systematic literature search through September 2018 identified randomized trials studying these pharmacologic therapies for extended anticoagulation following VTE. Treatment effects were calculated using network meta-analysis with frequentist fixed-effects model. RESULTS: 18 trials (18,221 patients) were included in the analysis. All treatments reduced the risk of recurrence compared to placebo/observation. Nonetheless, VKA (RR 0.22; 95%CI 0.13-0.39) and DOAC (RRs ranging from 0.25-0.32; 95%CI ranging from 0.13-0.52) were more effective than aspirin, whereas low-dose VKA was less effective than standard-dose VKA (RR 2.47; 95%CI 1.34-4.55). The efficacy of DOAC was globally comparable to standard-adjusted dose VKA. Low- (RR 3.13; 95%CI 1.37-7.16) and standard-dose (RR 3.23; 95%CI 1.16-8.99) VKA also increased the risk of MB, which was not the case for any DOAC. Low-dose VKA and low-dose DOAC had similar effects on MB compared to standard-doses. Although there was a trend for reduced MB and enhanced net clinical benefit for DOAC compared to VKA, this was not statistically significant. The specific anticoagulant therapies had no significant effects on deaths. CONCLUSION: Standard-dose VKA and low/standard-dose DOAC share similar effects on VTE recurrence and MB, whereas aspirin and low-dose VKA were associated with lower benefit/risk ratio.

Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis.

OBJECTIVE: Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD. METHODS: Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2 > 50%). RESULTS: Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5 ±â€¯5.5 years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5-93.6; 7 studies, n = 124) for corticosteroids alone, 80.7% (95%CI 49.6-94; 6 studies, n = 38) for cyclosporine A, 64.1% (95%CI 46.3-78.7; 4 studies, n = 32) for azathioprine, 86.2% (95%CI 61.5-96; 2 studies, n = 23) for tacrolimus, 56.4% (95%CI 44-68.0; 8 studies, n = 71) for cyclophosphamide, and 76.6% (95%CI 50.4-96.0; 2 studies, n = 20) for rituximab. In RP-ILD, survival rates at 3 months were 51.7% (95%CI 24.2-78.1; 2 studies, n = 11) for corticosteroids alone, 69.2% (95%CI 55.0-80.5; 8 studies, n = 146) for cyclosporine A and 72.4% (95%CI 6.4-99.0, 2 studies, n = 16) for cyclophosphamide. CONCLUSION: Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence.

Mortality in systemic necrotizing vasculitides: A retrospective analysis of the French Vasculitis Study Group registry.

OBJECTIVE: The aim of the study was to describe the evolution of mortality and cause-specific mortality over time in patients with systemic necrotizing vasculitides (SNV), including polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Patients with SNV from the French Vasculitis Study Group registry were divided into 5 groups according to the date of diagnosis: <1980, 1980-1989, 1990-1999, 2000-2010, and ≥ 2010. The causes of death were classified as vasculitis, infection, cardiovascular, malignancy, miscellaneous, or unknown. RESULTS: Among the 2217 patients included (PAN 16.1%, GPA 41.7%, EGPA 22.6%, MPA 19.6%), overall incidence of death was 2.26 per 100 person-years. The overall survival improved during each period considered. The 5-year survival rate increased from 72.2% (95% confidence interval [CI] 59.7-87.2) for patients diagnosed before 1980 to 94.5% (95% CI 90.4-98.8) after 2010 (p < 0.001). Periods of diagnosis, age, and male gender were independently associated with a poor survival with a non-significant difference between vasculitis. The incidence of mortality between the 1980s and after 2010 significantly decreased for vasculitis-related (p = 0.03) and cardiovascular-related deaths (p = 0.04). Incidence of death by infection remained stable between the 1980s and the 2000s but no death by infection occurred after 2010. The incidence of death by malignancy remained stable over time. CONCLUSION: Overall survival of SNV patients has improved since the 1980s with the decrease of vasculitis- and cardiovascular-related deaths, but cancer-related mortality remained stable. These results highlight malignancy as the current target to improve the overall prognosis.

Isolated positive anti-SS-B autoantibodies are not related to clinical features of systemic autoimmune diseases: Results from a routine population survey.

OBJECTIVE: To assess in clinical practice the frequency and diagnosis associated with the SS-B-positive/SS-A negative autoantibody profile. METHODS: We analyzed a one-year consecutive population of 624 patients referred by clinicians to the immunology laboratory to investigate anti-SS-A and/or anti-SS-B autoantibodies, who were detected using luminex technology. Data were analyzed for patients with isolated anti-SS-B autoantibodies. The clinical characteristics and diagnosis of connective tissue diseases (CTD) were retrieved according to the international criteria. RESULTS: Among 1173 sera positive for anti-SS-A and/or anti-SS-B autoantibodies from 624 patients, we identified 84 patients (13.5%) that had isolated anti-SS-B. Among the 75 patients positive for anti-SS-B with known clinical data, 15 were diagnosed with a CTD (20%) including 4 systemic lupus erythematosus (5%), 4 rheumatoid arthritis (5%), 2 idiopathic inflammatory myositis (3%), 1 primary Sjögren's syndrome pSS (1%), 1 systemic sclerosis (1%), 2 undefined CTD (3%), and 1 mixed CTD (1%). Among the 60 other patients, 18 had non-CTD autoimmune diseases and 42 had non-autoimmune diseases. Within the CTD population, the presence of isolated anti-SS-B was not significantly associated to characteristic indicating a specific syndrome. There was no association between diagnosis of CTD and level of anti-SS-B autoantibodies (p = 0.70). Arthralgia was the more frequent sign and encountered in 10 patients (67%), of whom 3 had arthritis. CONCLUSION: The presence of anti-SS-B, without anti-SS-A autoantibodies using luminex technology, was not associated with CTD, especially pSS, in daily clinical practice. Our data suggests that the SS-B serological profile is not contributive for the classification criteria of pSS.